PROJECT DESCRIPTION TEX-VAL: Texas A&M Tissue Chip Validation Center This proposal is to establish a Tissue Chip Validation Center at Texas A&M University (TEX-VAL) which will conduct testing of the microphysiological systems developed by NIH grantees. Our goal is to provide resources, personnel and infrastructure for establishing functionality, reproducibility, robustness and reliability of 8-12 tissue chip models that will represent a wide array of human organ and tissue systems. To achieve this goal we have assembled a team of 7 outstanding investigators who specialize in toxicology, in vitro and in vivo testing, microscopy, genomics, pharmacokinetic modeling, bioengineering, analytical chemistry and risk assessment. These investigators will closely oversee a team of highly qualified staff members who, in collaboration with tissue chip developers, will conduct validation experiments, analyze data, generate detailed reports and ensure that the data are available to the NIH Tissue Chip Program through an accessible database. Quality management plan and quality assurance project plans will be developed and overseen by a staff member with experience in these procedures and applicable regulations. All experimental protocols and data records will adhere to the highest standards based on the existing Organization for Economic Cooperation and Development (OECD) guidance for describing non-guideline in vitro test methods, as well as appropriate guidance on validation of alternatives to animal methods from the Food and Drug Administration and the National Toxicology Program. The TEX-VAL Center will utilize Texas A&M University's existing extensive infrastructure for medium- and high-throughput in vitro screening and high-content imaging at the Institute for Biosciences and Technology (Houston, TX) and College of Veterinary Medicine and Biomedical Sciences (College Station, TX), analytical chemistry at the Geosciences and Environmental Research Group (College Station, TX), and bioengineering and microfluidics at the NanoBio Systems Laboratory (College Station, TX). TEX-VAL Center will engage with the NIH tissue chip grantees and the IQ Consortium, as well as additional experts in the pharmaceutical and chemical industry, government agencies and academia to address questions on tissue chip validation, in vitro to in vivo concordance, untargeted metabolomics analyses, selection of appropriate cell types, experimental protocols, or selection of appropriate test compounds and positive and negative controls. The laboratories and investigators involved in the TEX-VAL have decades of experience with rigor, reproducibility and replication of data through multi-disciplinary research collaborations and service contracts with industry, state and federal government, and academic collaborators. In addition, TEX-VAL has an extensive network of partnerships with regulatory agencies in the USA and Europe already in place, which will serve as an important channel for engagement with diverse stakeholders to communicate the scientific promise and technical robustness, as well as any important limitations, of the tested tissue chips.